One-year follow-up after standardized perineal reconstruction in women with deficient perineum after vaginal delivery.

INTRODUCTION: Perineal tears are common after childbirth and, if not surgically repaired, they may result in a deficient perineum that can cause symptoms of pelvic floor dysfunction. Perineal reconstruction aims to restore the perineal body and increase the support of the pelvic floor. The objective of the present study was to estimate symptom reduction after perineal reconstruction in patients with deficient perineum after vaginal delivery and to compare outcomes between participants with or without concomitant levator ani muscle deficiency. MATERIAL AND METHODS: Participants presenting at the Karolinska Pelvic Floor Center with symptoms of deficient perineum at least 1 year after vaginal birth were invited to the study. Inclusion criteria were a visible perineal scar and confirmed anatomic defect. Levator ani defects were assessed using the Levator Ani Deficiency score. A perineal reconstruction was performed in a standardized way. Subjective symptoms were evaluated using the validated "Karolinska Symptoms After Perineal Tear Inventory" at baseline and 1-year follow-up. A score difference in the symptom of an acquired sensation of a wide vagina was the primary outcome. Results were stratified by the presence or absence of a levator ani deficiency. RESULTS: A perineal reconstruction was performed in 131 patients and 128 patients completed the Karolinska Symptoms After Perineal Tear Inventory at baseline and 119 at follow-up. Median age was 36.1 (interquartile range [IQR] 7.9), median body mass index 22.3 (IQR 5.1) and a median of two vaginal deliveries. Fifty-four women (41.2%) had a levator ani deficiency. The mean score reduction for the item "Do you feel that your vagina is too wide/loose?" was -1.56 (SD 0.96; P < 0.001) from a mean score of 2.75 (maximum 3) at baseline. The mean total score reduction was -9.1 points (SD 5.3; P < 0.001) from a mean score of 18.4 (maximum 33) points at baseline. There were no significant differences between groups when stratifying by levator ani deficiency. CONCLUSIONS: Our results show that perineal reconstructive surgery significantly decreases symptoms of deficient perineum after vaginal delivery. A concomitant levator ani defect does not affect the symptom reduction of an acquired sensation of a wide vagina or the total score reduction after surgery.

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h2g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h2g = 10.6%). The genetic correlation (rg) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h2g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

Agreement between asthma questionnaire and health care register data.

PURPOSE: Risk factors and consequences of asthma can be studied by using validated questionnaires. The overall objective of this study was to assess the agreement of parental-reported asthma-related questions regarding their children against Swedish health care registers. METHODS: We linked a population-based twin cohort of 27 055 children aged 9 to 12 years to the Swedish Prescribed Drug Register, National Patient Register, and the primary care register. Parent-reported asthma was obtained from questionnaires, and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen's kappa was estimated. RESULTS: The kappa of the "reported ever asthma" against a "register-based ever asthma" was 0.69 and 0.57 between the parental-"reported doctor's diagnosis" and "register-based doctor's diagnosis." The highest agreement between "reported current asthma" and "register-based current asthma" with at least 1 dispensed medication or a diagnosis applied to different time windows was seen for an 18-month window (kappa = 0.70). CONCLUSIONS: We found that parent-reported asthma-related questions showed on average good agreement with the Swedish health care registers. This implies that in-depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.